The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
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DOI：
10.1371/journal.pone.0256238
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Hay N
中科院分区：
文献类型：
--
作者：
Alasady MJ;Terry AR;Pierce AD;Cavalier MC;Blaha CS;Adipietro KA;Wilder PT;Weber DJ;Hay N
S100B在恶性黑色素瘤中经常升高。本研究揭示了一种调节机制，即S100B的升高降低了白介素6(IL6)的mRNA和蛋白水平，并抑制了IL6激活STAT3信号的自分泌环路。我们的结果表明S100B在转录水平上影响IL6的表达。S100B与P90核糖体S6激酶(RSK)形成钙依赖蛋白复合体，进而将RSK隔离到细胞质中。一直以来，抑制S100B被发现可以恢复定位于核的RSK底物CREB的磷酸化，CREB是IL6表达的有效转录因子。因此，在恶性黑色素瘤中，升高的S100B通过RSK信号通路减少IL6-STAT3信号。事实上，恶性黑色素瘤细胞系中S100B水平的升高与IL6和p-STAT3的低水平相对应。
S100B is frequently elevated in malignant melanoma. A regulatory mechanism was uncovered here in which elevated S100B lowers mRNA and secreted protein levels of interleukin-6 (IL6) and inhibits an autocrine loop whereby IL6 activates STAT3 signaling. Our results showed that S100B affects IL6 expression transcriptionally. S100B was shown to form a calcium-dependent protein complex with the p90 ribosomal S6 kinase (RSK), which in turn sequesters RSK into the cytoplasm. Consistently, S100B inhibition was found to restore phosphorylation of a nuclear located RSK substrate, CREB, which is a potent transcription factor for IL6 expression. Thus, elevated S100B reduces IL6-STAT3 signaling via RSK signaling pathway in malignant melanoma. Indeed, the elevated S100B levels in malignant melanoma cell lines correspond to low levels of IL6 and p-STAT3.
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